Proteomic profiling and genome-wide mapping of O-GlcNAc chromatin-associated proteins reveal an O-GlcNAc-regulated genotoxic stress response
| Autor: | Qiushi Chen, Xueqin Xie, Yubo Liu, Keren Zhang, Yan Ren, Yu Cao, Nana Zhang, Tongyi Dou, Yimin Liu, Kun Li, Wenli Li, Xinya Hao, Jianing Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Proteomics
0301 basic medicine Science Glycobiology General Physics and Astronomy Cellular homeostasis Genotoxic Stress Biology Article General Biochemistry Genetics and Molecular Biology Stress signalling 03 medical and health sciences 0302 clinical medicine NRF1 Enhancer lcsh:Science Transcription factor Regulation of gene expression Multidisciplinary General Chemistry Gene expression profiling Chromatin Cell biology carbohydrates (lipids) 030104 developmental biology lcsh:Q 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | O-GlcNAc modification plays critical roles in regulating the stress response program and cellular homeostasis. However, systematic and multi-omics studies on the O-GlcNAc regulated mechanism have been limited. Here, comprehensive data are obtained by a chemical reporter-based method to survey O-GlcNAc function in human breast cancer cells stimulated with the genotoxic agent adriamycin. We identify 875 genotoxic stress-induced O-GlcNAc chromatin-associated proteins (OCPs), including 88 O-GlcNAc chromatin-associated transcription factors and cofactors (OCTFs), subsequently map their genomic loci, and construct a comprehensive transcriptional reprogramming network. Notably, genotoxicity-induced O-GlcNAc enhances the genome-wide interactions of OCPs with chromatin. The dynamic binding switch of hundreds of OCPs from enhancers to promoters is identified as a crucial feature in the specific transcriptional activation of genes involved in the adaptation of cancer cells to genotoxic stress. The OCTF nuclear factor erythroid 2-related factor-1 (NRF1) is found to be a key response regulator in O-GlcNAc-modulated cellular homeostasis. These results provide a valuable clue suggesting that OCPs act as stress sensors by regulating the expression of various genes to protect cancer cells from genotoxic stress. Protein O-GlcNAcylation is involved in regulating gene expression and maintaining cellular homeostasis. Here, the authors develop a chemical reporter-based strategy for the proteomic profiling and genome-wide mapping of genotoxic stress-induced O-GlcNAcylated chromatin-associated proteins. |
| Databáze: | OpenAIRE |
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